Target (protein/gene) name: Trypanosoma cruzi, protein tyrosine phosphatase-like protein, putative NCBI Gene # or RefSeq#:TriTrypDB / Tc00.1047053506743.130GeneDB / Tc00.1047053506743.130 Protein ID (NP or XP#) or Wolbachia#: ID: 38485, XP_001611086.1 Organism (including strain): Trypanosoma cruzi Etiologic Risk Group: Risk Group 2 (RG2) - Parasitic Agents Background/Disease Information: Trypanosoma cruzi causes the trypanosomiasis disease, also known as Chagas disease, that can occur in humans and animals. The disease is transmitted by the reduviid bug when it deposits feces on the skin and bites, by ingesting certain foods with the parasite and by a mother passing the disease to her fetus . The feces are the penetrated when the infected area is scratched. There are two forms of this disease that can be found either in the blood or in the tissues. Once infected the trypanosomiasis disease can take decades to develop several symptoms such as internal organ damage of the heart, colon, esophagus and peripheral nervous system, which all can then lead to heart failure. But normally swelling occurs at the site of infections so patients are treated to antiparastic with a 60-90% cure rate. Once diagnosed with this disease, 4-8 weeks later they enter the chronic phase of the disease and 20-40% develop life-threating heart and/or digestive system disorders. The antiparastic treatments available are benznidazole and nifurtimox; side effects including brain toxicity, skin disorders and digestive system irritation.
The trypanosomiasis/Chagas disease is most common in poor, rural areas in the Americas especially in Mexico, Central America and South America. 11 million people have been estimated in these three areas to have this disease. The disease has become widespread in the Americas by the movement from rural to urban areas thus increasing the distribution of the disease. In order to stop the spread of this disease the triatomine insect vector needs to be eliminated and transmission from other sources needs to be prevented.
The process of this infection starts with depositing feces and taking blood. Then they reproduce by binary fission and move to the rectal wall where they become infectious, known as metacyclic trypomastigotes. The trypomastigotes, feces, enter the body and “swim” to the host cell using flagella and invade the cell becoming amastigotes. They then reproduce by binary fission and pseudocysts are formed causing the cell to burst once the amastigotes turn back into trypomastigotes. After the cell bursts the trypomastigotes infect other cells or eaten by other reduviid bugs. Essentiality of this protein:
significant loss of fitness in bloodstream forms (3 days) from a study of an African trypanosome [alsford]
significant loss of fitness in bloodstream forms (6 days) from a study of an African trypanosome [alsford]
significant gain of fitness in procyclic forms from a study of an African trypanosome [alsford] Complex of enzymes: No Druggable Targets: Protein-tyrosine phosphatase 4A3 http://www.ncbi.nlm.nih.gov/pubmed/18358718 http://www.ncbi.nlm.nih.gov/pubmed/16530413 EC#: 3.1.3.48 Link to BRENDA EC# page: http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.1.3.48 Enzyme Assay Information: there is no enzyme assay information on the TDR targets website, but according to this article http://europepmc.org/abstract/MED/3080918/reload=0;jsessionid=MJULYddg5wBO9je1AfXa.4 an enzyme assay that could potentially work is ELISA. Structure Available:
-there is not PDB available
- Homology Model:
---- Query Coverage: 87%
---- Max % Identities: 55%
---- % Positives: 69%
---- Chain used for homology: Chain A
Current Inhibitors: 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, THIOSULFATE Expression Information (has it been expressed in bacterial cells): E. coli Purification Method: there is no purification method Image of protein (PyMol with features delineated and shown separately):
Protein Tyrosine Phosphatase (Putative) From Leishmania Major
*Amino Acid Sequence (paste as text only - not as screenshot or as 'code'):
MGANGTLVECRRGESDAVVFRFLIFDAPSPSSVTAYVKLMQRYNVRQIVRACGQTYSAEA
FEKQGMVVHGWSFDDGAPPTQTVIDNWLNLLEQEKNKSPPETIAVHCVAGLGRAPILVAL
ALVEYGGMPPLDAVGYVRGRRKGAINQVQLNWLMRYKPRHQESNEGSLSCAGCAVM *length of your protein in Amino Acids: 176 aa Molecular Weight of your protein in kiloDaltons using the Expasy ProtParamwebsite: 19314.1 Molar Extinction coefficient of your protein at 280 nm wavelength: 25690 TMpred graph Image (http://www.ch.embnet.org/software/TMPRED_form.html). Input your amino acid sequence to it. *CDS Gene Sequence (paste as text only): ATGGGGGCCAACGGCACGCTGGTGGAGTGCAGGCGCGGGGAGTCCGACGCTGTTGTCTTCCGCTTCCTCA TATTTGACGCCCCGTCGCCCAGCAGCGTCACCGCGTATGTCAAGTTGATGCAGAGGTACAACGTGAGGCA AATTGTGCGGGCATGTGGCCAGACGTACAGTGCGGAGGCTTTTGAAAAGCAGGGAATGGTGGTGCACGGC TGGAGCTTTGACGACGGTGCCCCACCAACGCAGACCGTCATTGACAATTGGCTGAATTTGCTCGAACAGG AGAAGAACAAGTCACCCCCAGAGACGATTGCCGTGCACTGCGTTGCTGGACTTGGCCGAGCACCCATTTT GGTTGCGCTGGCACTTGTGGAGTACGGCGGAATGCCGCCACTCGACGCGGTGGGTTACGTGCGAGGACGG CGCAAAGGCGCCATCAATCAGGTGCAGCTCAACTGGCTTATGCGTTATAAACCGCGTCATCAGGAGAGTA ATGAGGGGTCTTTGAGTTGCGCGGGGTGTGCGGTCATGTAG *GC% Content for gene: 59%
NCBI Gene # or RefSeq#: TriTrypDB / Tc00.1047053506743.130 GeneDB / Tc00.1047053506743.130
Protein ID (NP or XP#) or Wolbachia#: ID: 38485, XP_001611086.1
Organism (including strain): Trypanosoma cruzi
Etiologic Risk Group: Risk Group 2 (RG2) - Parasitic Agents
Background/Disease Information:
Trypanosoma cruzi causes the trypanosomiasis disease, also known as Chagas disease, that can occur in humans and animals. The disease is transmitted by the reduviid bug when it deposits feces on the skin and bites, by ingesting certain foods with the parasite and by a mother passing the disease to her fetus . The feces are the penetrated when the infected area is scratched. There are two forms of this disease that can be found either in the blood or in the tissues. Once infected the trypanosomiasis disease can take decades to develop several symptoms such as internal organ damage of the heart, colon, esophagus and peripheral nervous system, which all can then lead to heart failure. But normally swelling occurs at the site of infections so patients are treated to antiparastic with a 60-90% cure rate. Once diagnosed with this disease, 4-8 weeks later they enter the chronic phase of the disease and 20-40% develop life-threating heart and/or digestive system disorders. The antiparastic treatments available are benznidazole and nifurtimox; side effects including brain toxicity, skin disorders and digestive system irritation.
The trypanosomiasis/Chagas disease is most common in poor, rural areas in the Americas especially in Mexico, Central America and South America. 11 million people have been estimated in these three areas to have this disease. The disease has become widespread in the Americas by the movement from rural to urban areas thus increasing the distribution of the disease. In order to stop the spread of this disease the triatomine insect vector needs to be eliminated and transmission from other sources needs to be prevented.
The process of this infection starts with depositing feces and taking blood. Then they reproduce by binary fission and move to the rectal wall where they become infectious, known as metacyclic trypomastigotes. The trypomastigotes, feces, enter the body and “swim” to the host cell using flagella and invade the cell becoming amastigotes. They then reproduce by binary fission and pseudocysts are formed causing the cell to burst once the amastigotes turn back into trypomastigotes. After the cell bursts the trypomastigotes infect other cells or eaten by other reduviid bugs.
Essentiality of this protein:
significant loss of fitness in bloodstream forms (3 days) from a study of an African trypanosome [alsford]
significant loss of fitness in bloodstream forms (6 days) from a study of an African trypanosome [alsford]
significant gain of fitness in procyclic forms from a study of an African trypanosome [alsford]
Complex of enzymes: No
Druggable Targets: Protein-tyrosine phosphatase 4A3
http://www.ncbi.nlm.nih.gov/pubmed/18358718
http://www.ncbi.nlm.nih.gov/pubmed/16530413
EC#: 3.1.3.48
Link to BRENDA EC# page: http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.1.3.48
Enzyme Assay Information: there is no enzyme assay information on the TDR targets website, but according to this article http://europepmc.org/abstract/MED/3080918/reload=0;jsessionid=MJULYddg5wBO9je1AfXa.4 an enzyme assay that could potentially work is ELISA.
Structure Available:
-there is not PDB available
- Homology Model:
---- Query Coverage: 87%
---- Max % Identities: 55%
---- % Positives: 69%
---- Chain used for homology: Chain A
Current Inhibitors:
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, THIOSULFATE
Expression Information (has it been expressed in bacterial cells): E. coli
Purification Method: there is no purification method
Image of protein (PyMol with features delineated and shown separately):
Protein Tyrosine Phosphatase (Putative) From Leishmania Major
*Amino Acid Sequence (paste as text only - not as screenshot or as 'code'):
MGANGTLVECRRGESDAVVFRFLIFDAPSPSSVTAYVKLMQRYNVRQIVRACGQTYSAEA
FEKQGMVVHGWSFDDGAPPTQTVIDNWLNLLEQEKNKSPPETIAVHCVAGLGRAPILVAL
ALVEYGGMPPLDAVGYVRGRRKGAINQVQLNWLMRYKPRHQESNEGSLSCAGCAVM
*length of your protein in Amino Acids: 176 aa
Molecular Weight of your protein in kiloDaltons using the Expasy ProtParamwebsite: 19314.1
Molar Extinction coefficient of your protein at 280 nm wavelength: 25690
TMpred graph Image (http://www.ch.embnet.org/software/TMPRED_form.html). Input your amino acid sequence to it.
*CDS Gene Sequence (paste as text only):
ATGGGGGCCAACGGCACGCTGGTGGAGTGCAGGCGCGGGGAGTCCGACGCTGTTGTCTTCCGCTTCCTCA TATTTGACGCCCCGTCGCCCAGCAGCGTCACCGCGTATGTCAAGTTGATGCAGAGGTACAACGTGAGGCA AATTGTGCGGGCATGTGGCCAGACGTACAGTGCGGAGGCTTTTGAAAAGCAGGGAATGGTGGTGCACGGC TGGAGCTTTGACGACGGTGCCCCACCAACGCAGACCGTCATTGACAATTGGCTGAATTTGCTCGAACAGG AGAAGAACAAGTCACCCCCAGAGACGATTGCCGTGCACTGCGTTGCTGGACTTGGCCGAGCACCCATTTT GGTTGCGCTGGCACTTGTGGAGTACGGCGGAATGCCGCCACTCGACGCGGTGGGTTACGTGCGAGGACGG CGCAAAGGCGCCATCAATCAGGTGCAGCTCAACTGGCTTATGCGTTATAAACCGCGTCATCAGGAGAGTA ATGAGGGGTCTTTGAGTTGCGCGGGGTGTGCGGTCATGTAG
*GC% Content for gene: 59%
Resource Websites:
http://www.tdrtargets.org/targets/view?gene_id=38485
http://en.wikipedia.org/wiki/Trypanosoma_cruzi
http://blast.ncbi.nlm.nih.gov/Blast.cgi#alnHdr_340708234
http://www.bindingdb.org/bind/luceneResult.jsp?thisInput=Trypanosoma+cruzi%2C+protein+tyrosine+phosphatase-like+protein%2C+putative+&submit=Go
http://brenda-enzymes.org/php/result_flat.php4?ecno=3.1.3.48
http://www.sciencedirect.com/science/article/pii/S09680890801002X
http://www.utexas.edu/research/rsc/ibc/agent_class.html
http://www.rcsb.org/pdb/explore/explore.do?structureId=3S4O